The antitumor effect of local tumor hyperthermia was evaluated alone and in combination with antitumor agents. Specially formulated heat-labile liposomes with encapsulated methotrexate were used to enhance the local accumulation of methotrexate in tumors by combination with local tumor hyperthermia. The adenosine deaminase inhibitor, 2'-dexycoformycin, was found to potentiate the cytotoxic effects and antitumor activity of several adenosin analogs that are substrates for adenosine deaminase and that are inactivated by his enzyme. In addition, although neither adenosine nor 2'-deoxyadenosine have antitumor activity per se, when combined with 2'-deoxycoformycin, 2'-deoxyadenosine exhibited antileukemic activity in murine leukemia P388. The antitumor activity of nitrogen mustard and adriamycin was not affected by prior administration of various nucleophiles.